Genetic characterization of Greek population isolates reveals strong genetic drift at missense and trait-associated variants

Kalliope Panoutsopoulou, Konstantinos Hatzikotoulas, Dionysia Kiara Xifara, Vincenza Colonna, Aliki-Eleni Farmaki, Graham R. S. Ritchie, Lorraine Southam, Arthur Gilly, Ioanna Tachmazidou, Segun Fatumo, Angela Matchan, Nigel W. Rayner, Ioanna Ntalla, Massimo Mezzavilla, Yuan Chen, Chrysoula Kiagiadaki, Eleni Zengini, Vasiliki Mamakou, Antonis Athanasiadis, Margarita Giannakopoulou, Vassiliki-Eirini Kariakli, Rebecca N. Nsubuga, Alex Karabarinde, Manjinder Sandhu, Gil McVean, Chris Tyler-Smith, Emmanouil Tsafantakis, Maria Karaleftheri, Yali Xue, George Dedoussis and Eleftheria Zeggini ()
Additional contact information
Kalliope Panoutsopoulou: Wellcome Trust Sanger Institute
Konstantinos Hatzikotoulas: Wellcome Trust Sanger Institute
Dionysia Kiara Xifara: Wellcome Trust Centre for Human Genetics, University of Oxford
Vincenza Colonna: Institute of Genetics and Biophysics ‘A. Buzzati-Traverso’, National Research Council (CNR)
Aliki-Eleni Farmaki: Harokopio University of Athens
Graham R. S. Ritchie: Wellcome Trust Sanger Institute
Lorraine Southam: Wellcome Trust Sanger Institute
Arthur Gilly: Wellcome Trust Sanger Institute
Ioanna Tachmazidou: Wellcome Trust Sanger Institute
Segun Fatumo: Wellcome Trust Sanger Institute
Angela Matchan: Wellcome Trust Sanger Institute
Nigel W. Rayner: Wellcome Trust Sanger Institute
Ioanna Ntalla: Harokopio University of Athens
Massimo Mezzavilla: Wellcome Trust Sanger Institute
Yuan Chen: Wellcome Trust Sanger Institute
Chrysoula Kiagiadaki: Anogia Medical Centre
Eleni Zengini: Dromokaiteio Psychiatric Hospital of Athens, Chaidari, Athens 12461, Greece
Vasiliki Mamakou: Dromokaiteio Psychiatric Hospital of Athens, Chaidari, Athens 12461, Greece
Antonis Athanasiadis: Echinos Medical Centre
Margarita Giannakopoulou: School of Health Sciences, Faculty of Nursing, National and Kapodistrian University of Athens, Goudi, Athens 11527, Greece
Vassiliki-Eirini Kariakli: Harokopio University of Athens
Rebecca N. Nsubuga: Medical Research Council/Uganda Virus Research Institute, Uganda Research Unit on AIDS
Alex Karabarinde: Medical Research Council/Uganda Virus Research Institute, Uganda Research Unit on AIDS
Manjinder Sandhu: Wellcome Trust Sanger Institute
Gil McVean: Wellcome Trust Centre for Human Genetics, University of Oxford
Chris Tyler-Smith: Wellcome Trust Sanger Institute
Emmanouil Tsafantakis: Anogia Medical Centre
Maria Karaleftheri: Echinos Medical Centre
Yali Xue: Wellcome Trust Sanger Institute
George Dedoussis: Harokopio University of Athens
Eleftheria Zeggini: Wellcome Trust Sanger Institute

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract Isolated populations are emerging as a powerful study design in the search for low-frequency and rare variant associations with complex phenotypes. Here we genotype 2,296 samples from two isolated Greek populations, the Pomak villages (HELIC-Pomak) in the North of Greece and the Mylopotamos villages (HELIC-MANOLIS) in Crete. We compare their genomic characteristics to the general Greek population and establish them as genetic isolates. In the MANOLIS cohort, we observe an enrichment of missense variants among the variants that have drifted up in frequency by more than fivefold. In the Pomak cohort, we find novel associations at variants on chr11p15.4 showing large allele frequency increases (from 0.2% in the general Greek population to 4.6% in the isolate) with haematological traits, for example, with mean corpuscular volume (rs7116019, P=2.3 × 10−26). We replicate this association in a second set of Pomak samples (combined P=2.0 × 10−36). We demonstrate significant power gains in detecting medical trait associations.

Date: 2014
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DOI: 10.1038/ncomms6345

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